Determinants of the diminished exercise capacity in patients with chronic obstructive pulmonary disease: looking beyond the lungs

Abstract

Key points: Peak oxygen uptake, a primary determinant of prognosis, mortality and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD), with mounting evidence supporting an important role for peripheral dysfunction, particularly within skeletal muscle. In patients with severe COPD and activity-matched controls, muscle oxygen transport and utilization were assessed at peak effort during single-leg knee-extensor exercise (KE), where ventilation is assumed to be submaximal. This strategy removes ventilation as the major constraint to exercise capacity in COPD, allowing maximal muscle function to be attained and evaluated. During maximal KE, both convective arterial oxygen delivery to the skeletal muscle microvasculature and subsequent diffusive oxygen delivery to the mitochondria were diminished in patients with COPD compared to control subjects. These findings emphasize the importance of factors, beyond the lungs, that influence exercise capacity in this patient population and may, ultimately, influence the prognosis, mortality and quality of life for patients with COPD.

Abstract: Peak oxygen uptake ( ${\dot{V}}_{O_2\mathrm{peak}}$ ), a primary determinant of prognosis, mortality and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD). Mounting evidence supports an important role of the periphery, particularly skeletal muscle, in the diminished ${\dot{V}}_{O_2\mathrm{peak}}$ with COPD. However, the peripheral determinants of ${\dot{V}}_{O_2\mathrm{peak}}$ have not been comprehensively assessed in this cohort. Thus, the hypothesis was tested that both muscle convective and diffusive oxygen (O₂ ) transport, and therefore skeletal muscle peak O₂ uptake ( ${\dot{V}}_{M{O}_2\mathrm{peak}}$ ), are diminished in patients with COPD compared to matched healthy controls, even when ventilatory limitations (i.e. attainment of maximal ventilation) are minimized by using small muscle mass exercise. Muscle O₂ transport and utilization were assessed at peak exercise from femoral arterial and venous blood samples and leg blood flow (by thermodilution) in eight patients with severe COPD (forced expiratory volume in 1s (FEV₁ ) ± SEM = 0.9 ± 0.1 l, 30% of predicted) and eight controls during single-leg knee-extensor exercise. Both muscle convective O₂ delivery (0.44 ± 0.06 vs. 0.69 ± 0.07 l min^-1 , P < 0.05) and muscle diffusive O₂ conductance (6.6 ± 0.8 vs. 10.4 ± 0.9 ml min^-1 mmHg^-1 , P < 0.05) were ∼1/3 lower in patients with COPD than controls, resulting in an attenuated ${\dot{V}}_{M{O}_2\mathrm{peak}}$ in the patients (0.27 ± 0.04 vs. 0.42 ± 0.05 l min^-1 , P < 0.05). When cardiopulmonary limitations to exercise are minimized, the convective and diffusive determinants of ${\dot{V}}_{M{O}_2\mathrm{peak}}$ , at the level of the skeletal muscle, are greatly attenuated in patients with COPD. These findings emphasize the importance of factors, beyond the lungs, that may ultimately influence this population's prognosis, mortality and quality of life.

Keywords: O2 delivery; O2 uptake; blood flow; lung disease.